The cytochromes (Cyts) are a group of chromophoric proteins that serve as electron carriers in the electron transport process of cells. The proteins convert the high-energy electrons derived from the metabolism of carbohydrates, fats, and other foodstuffs into ATP, the primary source of energy for driving a cell's many energy-requiring reactions. Cytochromes are related to one another by the presence of a bound heme group consisting of a porphyrin ring containing a tightly bound iron atom. The iron atom serves as the actual electron carrier by changing from the ferric to the ferrous state when accepting an electron. Cytochromes accept electrons from susbstrates such as NADH or FADH.sub.2 and pass them on to other electron carriers such as other cytochromes or ubiquinone.
Cyts are classified into subgroups a, b, and c, according to distinctive absorption spectra conferred on them by differences in their interactions with the heme group. These classifications are not functionally important. Cytochromes a, a.sub.3, b.sub.562, b.sub.566, c, and c.sub.1 are all components of the mammalian mitochondrial membrane respiratory chain involved in oxidative phosphorylation. Cyt b5 exists in both a membrane-bound form found in mitochondria and endoplasmic reticulum and a soluble form found in erythrocytes. The membrane-bound form has been linked with lipid and drug metabolism, and with NADPH-linked hydroxylation reactions (De Sylvestris, M. et al. (1995) FEBS Lett. 370:69-74; Ozols, J. (1989) Biochim. et Biophys. Acta 997:121-30). Cytochrome b5 from a variety of mammalian sources, including man, horse, rat, rabbit, and pig consists of a single polypeptide chain of approximately 135 amino acids that is folded into two structurally distinct domains (Ozols, J. (1989), supra). The N-terminal region from approximately residues 1-96 is a polar, catalytic domain to which the heme group is non-covalently attached. The C-terminal hydrophobic region, extending from approximately residue 96 to the end of the molecule, is a membrane-binding domain that anchors the polypeptide chain to the mitochondrial membrane. Studies with the rat cytochrome b5 also indicate that the targeting information for directing this protein to the mitochondrial membrane resides in the C-terminal sequence rather than in an N-terminal signal sequence as is common in other mitochondrial proteins (De Silvestris, et al., supra). Since the rat protein also lacks the N-terminal 30 amino acids found in most other mitochondrial isoforms, the catalytic region of these proteins is further defined as existing between residues 30 to 96. The soluble form of the human cytochrome b5 lacks the C-terminal membrane-binding region.
The discovery of a new cytochrome b5, and polynucleotides encoding it satisfy a need in the art by providing new compositions which are useful for the diagnosis, prevention, and treatment of cancer, myopathies, and developmental disorders.